Leptospirosis outcomes across a South East Asian cohort

ISRCTN	ISRCTN61089608
DOI	https://doi.org/10.1186/ISRCTN61089608
Sponsors	Nagasaki University, London School of Hygiene & Tropical Medicine
Funder	Nagasaki University

Submission date: 09/12/2025
Registration date: 11/12/2025
Last edited: 10/12/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Leptospirosis is the most common bacterial infection that spreads from animals to people worldwide. People can develop a range of symptoms, from none at all, to a mild flu-like illness, to severe disease which can cause inflammation throughout the body, leading to organ damage and death.

Leptospirosis particularly affects people living in low- and middle-income countries, where flooding, poor sanitation, and limited healthcare access make outbreaks more likely. Globally, it is estimated that about 1 million people get leptospirosis each year, and nearly 60,000 die from it. However, these numbers are uncertain because many countries do not regularly collect or report leptospirosis data. This means that there is still the lack a clear picture of how serious the problem is in many parts of the world. This study explores clinical presentations across three countries where leptospirosis is endemic.

- The Philippines, where frequent floods and typhoons, especially in Manila, often lead to outbreaks. In some areas, death rates can be very high — up to 40% during major outbreaks.

- Malaysia, which regularly experiences outbreaks across all states, with the disease becoming more common in recent years.

- Vietnam, where officially lists leptospirosis as a notifiable disease, but many cases are likely missed because the current system relies on clinical diagnosis without laboratory confirmation.

The aim of this study is to bring together data from all three countries to better understand how leptospirosis patients are treated and what outcomes they experience. The researchers aim to identify which factors are linked to severe illness or poor recovery.

Who can participate?
Participants of any age with a clinical or microbiological diagnosis of leptospirosis from a search of hospital records.

What does the study involve?
Data capture was from at least the first health services contact until the end of hospital contact or last study contact. Summary statistics were performed as well as risk analysis of epidemiological or clinical factors associated with primary outcomes.

What are the possible benefits and risks of participating?
The benefit of undertaking this study far outweighs the risks. Undertaking this study, and combining datasets, will lead to a better understand how leptospirosis is treated and which treatments are used in different settings. This study mainly involves reviewing information from medical records or data already available publicly that collected routine clinical data, so the risks are minimal.

Where is the study run from?
The study is jointly run by the London School of Hygiene and Tropical Medicine and Nagasaki University, but the collaborative site where data capture was completed was in Malaysia, Vietnam, and the Philippines.

When is the study starting and how long is it expected to run for?
December 2023 to August 2025.

Who is funding the study?
This research was partially funded by the Nagasaki University WISE Programme.

Who is the main contact?
Dr Nathaniel Lee, nathaniel.lee@doctors.org.uk, nathaniel.lee@lshtm.ac.uk

Contact information

Dr Nathaniel Lee
Public, Scientific, Principal investigator

London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom

ORCID ID	0000-0002-4393-6891
Phone	+44 (0)20 7636 8636
Email	nathaniel.lee@doctors.org.uk

Study information

Primary study design	Observational
Study design	Multicentre observational longitudinal cohort study
Secondary study design	Cohort study
Scientific title	The case burden, treatment strategies, and patient outcomes for Leptospirosis across South-East Asia; a multi-country cohort study
Study acronym	LEPCO
Study objectives	The primary objective was to explore the major clinical outcomes in the combined cohort to inform the evaluation of a future COS and therapeutic treatment trials. Secondary objectives included a) summaries of clinical characteristics, treatment regimens, and supportive management; and b) risk analysis of epidemiological or clinical factors potentially associated with clinical outcomes of interest.
Ethics approval(s)	1. Approved 08/01/2016, Research and Ethical Review Board of San Lazaro Hospital (San Lazaro Hospital, Quiricada Street, Manila, 1008, Philippines; +63 2 8732 3777; slh.iso.reru2@gmail.com), ref: Executive approval (electronic copy uploaded) 2. Approved 01/12/2019, Institutional Review Board of the Institute of Tropical Medicine (Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan; +8195-819-7803; soumu_nekken@ml.nagasaki-u.ac.jp), ref: 170707170 and 170707170-2 3. Approved 01/10/2019, Research and Ethical Review Board of San Lazaro Hospital (San Lazaro Hospital, Quiricada Street, Manila, 1008, Philippines; +63 2 8732 3777; slh.iso.reru2@gmail.com), ref: SLH-RERU-2015-005-E 4. Approved 01/10/2019, Institutional Review Board of the Institute of Tropical Medicine (Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan; +8195-819-7803; soumu_nekken@ml.nagasaki-u.ac.jp), ref: 150226136– 4 5. Approved 01/06/2012, The Institutional Review Board of Bach Mai Hospital (Bach Mai Hospital, Đ. Giải Phóng/78 Ng. 78 Đ. Giải Phóng, Phương Đình, Đống Đa, Hanoi, 100000, Viet Nam; +84 969 851 616; bnpham2018@gmail.com), ref: 15-IRB, 2011 6. Approved 01/06/2012, Institutional Review Board of the Institute of Tropical Medicine (Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan; +8195-819-7803; soumu_nekken@ml.nagasaki-u.ac.jp), ref: 12021085–4 7. Approved 14/04/2023, Medical Research Ethics Committee University of Malaya Medical Centre (Jln Profesor Diraja Ungku Aziz, Seksyen 13, Kuala Lumpur, 50603, Malaysia; 03-79493209/225; ummc-mrec@ummc.edu.my), ref: 2023215-12154 8. Approved 26/06/2023, London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Keppel Street, London, WC1E 7HT, United Kingdom; +4402076368363; ethics@lshtm.ac.uk), ref: 29255
Health condition(s) or problem(s) studied	Clinical characteristics, treatments, and outcomes of people seen at health institutions with leptospirosis
Intervention	Data capture for all participants was from at least the first health services contact until the end of hospital contact or last study contact. Summary statistics were performed as well as risk analysis of epidemiological or clinical factors associated with primary outcomes.
Intervention type	Other
Primary outcome measure(s)	All-cause mortality up to the latest follow-up time measured using using data collection from patient medical records at one time point
Key secondary outcome measure(s)	A composite outcome of severe disease including: biochemical evidence of single or multiple organ failure; development of pulmonary haemorrhage; the need for Intensive Treatment Unit (ITU) admission; need for renal replacement therapy (RRT); need for mechanical ventilation; need for oxygen supplementation; and the need for inotropic support or clinical evidence of haemodynamic compromise measured using using data collection from patient medical records at one time point Duration of hospitalization (days) measured using using data collection from patient medical records at one time point Duration of fever (days) measured using using data collection from patient medical records at one time point Hospital discharge measured using using data collection from patient medical records at one time point
Completion date	07/08/2025

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	1 Year
Upper age limit	87 Years
Sex	All
Target sample size at registration	3000
Total final enrolment	3052
Key inclusion criteria	Clinical or microbiological diagnosis of leptospirosis from a search of hospital records
Key exclusion criteria	For SLH2 dataset, the following exclusions were applied: 1. Hospitalization last 30 days 2. Fever onset > 48 hours post-hospitalization 3. Blood culture draw ≥ 48 hours after admission 4. Positive microbiological diagnosis of dengue at admission 5. Diagnosis of other viral infection and WBC ≤ 12,000/mm3 or ≥ 4,000 mm3 6. Known underlying chronic disease/condition 7. < 1 year old 8. Declined consent to participate For BMH1 the following exclusions were applied: 1. Clinical diagnosis of malaria, dengue, food-borne gastroenteritis, cellulitis, or rat-bite fever at admission 2. Microbiological diagnosis at source referral 3. Suspected of having hepatitis-related disease
Date of first enrolment	19/12/2023
Date of final enrolment	07/08/2025

Locations

Countries of recruitment

Malaysia
Philippines
Viet Nam

Study participating centres

University of Malaya Medical Center

Jln Profesor Diraja Ungku Aziz, Seksyen 13
Kuala Lumpur
50603
Malaysia

San Lazaro Hospital

Quiricada St, Santa Cruz
Manila
1003
Philippines

Bach Mai Hospital

Đ. Giải Phóng/78 Ng. 78 Đ. Giải Phóng, Phương Đình, Đống Đa
Hanoi
100000
Viet Nam

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Stored in publicly available repository
IPD sharing plan	The datasets generated during and/or analysed during the current study will be stored in a publicly available repository (LSHTM Data Repository; https://datacompass.lshtm.ac.uk/; or other suitable public repository)

Editorial Notes

09/12/2025: Study’s existence confirmed by the Medical Research Ethics Committee of The University of Malaya Medical Centre, Malaysia.